The research program seeks to define the role of acute pulmonary infections during early childhood in the pathogenesis of chronic respiratory diseases which may occur in later life. The problem is being approached through interrelated clinical (pediatrics, medical, epidemio/ogic, biostatistical) and basic (microbiological, immunologic, physiologic, pathologic) studies. The research of the component projects will: 1) seek sequelae of bronchiolitis, croup and bronchitis/pneumonia; 2) determine which kinds of pulmonary infections are of prime importance for targeting intervention efforts; 3) attempt to determine the interactive effects of host predisposition, infection and micro-environmental pollution in the causation of respiratory problems; 4) examine airways and lung cell injury by infectious agents, search for contributory host defects and analyze recovery patterns; and 5) use cell cultures and animal models to examine new therapeutic and prophylactic measure for acute bronchiolitis. Populations of children are being studied both prospectively and retrospectively using multiple regression and other statistical approaches to evaluate the impact of defined respiratory infections and other variables on subsequent pulmonary health. Ultrastructural physiologic and metabolic studies of human respiratory epithelial cells (normal and infected) are complemented by similar research on differentiated respiratory cell lines from animals. Synthetic protease inhibitors are being tested for their antiviral properties, and effects of viral antigenic variation on protective immunity will be assessed. Basic studies of the molecular biology are being made of two important respiratory pathogens, Mycoplasma pneumoniae and non-typable Haemophilus influenzae. Together these projects deal with one of the most common childhood problems and one of the more significant debilitating diseases of adults, with the ultimate goal of defining improved methods of diagnosis, treatment and prevention.